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Role of CagA in Helicobacter pylori Infection and Pathology

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The Biology of Gastric Cancers

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References

  • Ahmad, S., Banville, D., Zhao, Z., et al. 1993. A widely expressed human protein-tyrosine phos-phatase containing src homology 2 domains. Proc Natl Acad Sci USA 90:2197–2201.

    Article  CAS  PubMed  Google Scholar 

  • Amieva, M.R., Vogelmann, R., Covacci, A., et al. 2003. Disruption of the epithelial apical-junc-tional complex by Helicobacter pylori CagA. Science 300:1430–1434.

    Article  CAS  PubMed  Google Scholar 

  • Asahi, M., Azuma, T., Ito, S., et al. 2000. Helicobacter pylori CagA protein can be tyrosine phos-phorylated in gastric epithelial cells. J Exp Med 191:593–602.

    Article  CAS  PubMed  Google Scholar 

  • Azuma, T., Yamakawa, A., Yamazaki, S., et al. 2002. Correlation between variation of the 3'region of the cagA gene in Helicobacter pylori and disease outcome in Japan. J Infect Dis 186:1621–1630.

    Article  CAS  PubMed  Google Scholar 

  • Azuma, T., Yamazaki, S., Yamakawa, A., et al. 2004. Variation in the SHP-2 binding site of Helicobacter pylori CagA protein is associated with gastric atrophy and cancer. J Infect Dis 189:820–827.

    Article  CAS  PubMed  Google Scholar 

  • Backert, S., Moese, S., Selbach, M., et al. 2001. Phosphorylation of tyrosine 972 of the Helicobacter pylori CagA protein is essential for induction of a scattering phenotype in gastric epithelial cells. Mol Microbiol 42:631–644.

    Article  CAS  PubMed  Google Scholar 

  • Bagnoli, F., Buti, L., Tompkins, L., et al. 2005. Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. Proc Natl Acad Sci USA 102:16339–16344.

    Article  CAS  PubMed  Google Scholar 

  • Blaser, M.J., Perez-Perez, G.I., Kleanthous, H., et al. 1995. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 55:2111–2115.

    CAS  PubMed  Google Scholar 

  • Censini, S., Lange, C., Xiang, Z., et al. 1996. Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci USA 93:14648–14653.

    Article  CAS  PubMed  Google Scholar 

  • Churin, Y., Al-Ghoul, L., Kepp, O., et al. 2003. Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response. J Cell Biol 161:249–255.

    Article  CAS  PubMed  Google Scholar 

  • Correa, P. 1988. A human model of gastric carcinogenesis. Cancer Res 48:3554–3560.

    CAS  PubMed  Google Scholar 

  • Covacci, A., Censini, S., Bugnoli, M., et al. 1993. Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 90:5791–5795.

    Article  CAS  PubMed  Google Scholar 

  • Covacci, A., Telford, J.L., Del Giudice, G., et al. 1999. Helicobacter pylori virulence and genetic geography. Science 284:1328–1333.

    Article  CAS  PubMed  Google Scholar 

  • De Souza, D., Fabri, L.J., Nash, A., et al. 2002. SH2 domains from suppressor of cytokine signal-ing-3 and protein tyrosine phosphatase SHP-2 have similar binding specificities. Biochemistry 41:9229–9236.

    Article  PubMed  Google Scholar 

  • The Eurogast Study Group. 1993. An association between Helicobacter pylori infection and gastric cancer. Lancet 341:1359–1362.

    Article  Google Scholar 

  • Feng, G.S., Hui, C.C., Pawson, T. 1993. SH2-containing phosphotyrosine phosphatase as a target of protein-tyrosine kinases. Science 259:1607–1611.

    Article  CAS  PubMed  Google Scholar 

  • Freeman, R.M., Jr., Plutzky, J., Neel, B.G. 1992. Identification of a human src homology 2-con-taining protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. Proc Natl Acad Sci USA 89:11239–11243.

    Article  CAS  PubMed  Google Scholar 

  • Higashi, H., Tsutsumi, R., Fujita, A., et al. 2002a. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci USA 99:14428–14433.

    Article  CAS  Google Scholar 

  • Higashi, H., Tsutsumi, R., Muto, S., et al. 2002b. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 295:683–686.

    Article  CAS  Google Scholar 

  • Huang, J.Q., Zheng, G.F., Sumanac, K., et al. 2003. Meta-analysis of the relationship between cagA seropositivity and gastric cancer. Gastroenterology 125:1636–1644.

    Article  PubMed  Google Scholar 

  • IARC. 1994. Schistosomes, liver flukes and Helicobacter pylori. Monographs on the evaluation of carcinogenic risks to humans. IARC Sci Publ 61:1–241.

    Google Scholar 

  • Ito, Y., Azuma, T., Ito, S., et al. 1997. Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan. J Clin Microbiol 35:1710–1714.

    CAS  PubMed  Google Scholar 

  • Ito, S., Azuma, T., Murakita, H., et al. 1996. Profile of Helicobacter pylori cytotoxin derived from two areas of Japan with different prevalence of atrophic gastritis. Gut 39:800–806.

    Article  CAS  PubMed  Google Scholar 

  • Jackson, C.B., Judd, L.M., Menheniott, T.R., et al. 2007. Augmented gp130-mediated cytokine signalling accompanies human gastric cancer progression. J Pathol 213:140–151.

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi, S., Wada, O., Nakajima, T., et al. 1995. Serum anti-Helicobacter pylori antibody and gastric carcinoma among young adults. Research group on prevention of gastric carcinoma among young adults. Cancer 75:2789–2793.

    Article  CAS  PubMed  Google Scholar 

  • Kodama, A., Matozaki, T., Fukuhara, A., et al. 2000. Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth factor/scatter factor-induced cell scattering. Mol Biol Cell 11:2565–2575.

    CAS  PubMed  Google Scholar 

  • Mimuro, H., Suzuki, T., Tanaka, J., et al. 2002. Grb2 is a key mediator of Helicobacter pylori CagA protein activities. Mol Cell 10:745–755.

    Article  CAS  PubMed  Google Scholar 

  • Murata-Kamiya, N., Kurashima, Y., Teishikata, Y., et al. 2007. Helicobacter pylori CagA interacts with E-cadherin and deregulates the beta-catenin signal that promotes intestinal transdif-ferentiation in gastric epithelial cells. Oncogene 26:4617–4626.

    Article  CAS  Google Scholar 

  • Neel, B.G., Gu, H., Pao, L. 2003. The “Shp”ing news: SH2 domain-containing tyrosine phos-phatases in cell signaling. Trends Biochem Sci 28:284–293.

    Article  CAS  PubMed  Google Scholar 

  • Odenbreit, S., Puls, J., Sedlmaier, B., et al. 2000. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287:1497–1500.

    Article  CAS  PubMed  Google Scholar 

  • Parkin, D.M., Bray, F.I., Devesa, S.S. 2001. Cancer burden in the year 2000. The global picture. Eur J Cancer 37:S4–S66.

    Article  PubMed  Google Scholar 

  • Parsonnet, J., Friedman, G.D., Vandersteen, D.P., et al. 1991. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325:11127–11131.

    Article  Google Scholar 

  • Roovers, K., Assoian, R.K. 2000. Integrating the MAP kinase signal into the G1 phase cell cycle machinery. Bioessays 22:818–826.

    Article  CAS  PubMed  Google Scholar 

  • Saadat, I., Higashi, H., Obuse, C., et al. Helicobacter pylori CagA targets PAR1/MARK kinase to disrupt epithelial cell polarity. Nature 447:330–333.

    Google Scholar 

  • Satomi, S., Yamakawa, A., Matsunaga, S., et al. 2006. Relationship between the diversity of the cagA gene of Helicobacter pylori and gastric cancer in Okinawa, Japan. J Gastroenterol 41:668–673.

    Article  CAS  PubMed  Google Scholar 

  • Segal, E.D., Cha, J., Lo, J., et al. 1999. Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci USA 96:14559–14564.

    Article  CAS  PubMed  Google Scholar 

  • Segal, E.D., Falkow, S., Tompkins, L.S. 1996. Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell protein. Proc Natl Acad Sci USA 93:1259–1264.

    Article  CAS  PubMed  Google Scholar 

  • Selbach, M., Moese, S., Hauck, C.R., et al. 2002. Src is the kinase of the Helicobacter pylori CagA protein in vitro and in vivo. J Biol Chem 277:6775–6778.

    Article  CAS  PubMed  Google Scholar 

  • Stein, M., Bagnoli, F., Halenbeck, R., et al. 2002. c-Src/Lyn kinase activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol Microbiol 43:971–980.

    Article  CAS  PubMed  Google Scholar 

  • Stein, M., Rappuoli, R., Covacci, A. 2000. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after cag-driven host cell translocation. Proc Natl Acad Sci USA 97:1263–1268.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, M., Mimuro, H., Suzuki, T., et al. 2005. Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion. J Exp Med 202:1235–1247.

    Article  CAS  PubMed  Google Scholar 

  • Tomb, J.F., White, O., Kerlavage, A.R., et al. 1997. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature 388:539–547.

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi, R., Takahashi, A., Azuma, T., et al. 2006. FAK is a substrate and downstream effector of SHP-2 complexed with Helicobacter pylori CagA. Mol Cell Biol 26:261–276.

    Article  CAS  PubMed  Google Scholar 

  • van Doorn, L.J., Figueiredo, C., Megraud, F., et al. 1999. Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology 116:823–830.

    Article  PubMed  Google Scholar 

  • Yamaoka, Y., El-Zimaity, H.M., Gutierrez, O., et al. 1999. Relationship between the cagA 3′ repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology 117:342–349.

    Article  CAS  PubMed  Google Scholar 

  • Yamaoka, Y., Kodama, T., Kashima, K., et al. 1998. Variants of the 3′ region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol 36:2258–2263.

    CAS  PubMed  Google Scholar 

  • Yamazaki, S., Yamakawa, A., Ito, Y., et al. 2003. The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa. J Infect Dis 187:334–337.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Kobe University School of Medicine, Kobe, Japan

    Takeshi Azuma

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  1. Takeshi Azuma
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Editor information

Editors and Affiliations

  1. Division of Digestive and Liver Diseases, Columbia University, New York, NY, USA

    Timothy C. Wang (Silberberg Professor of Medicine Chair) (Silberberg Professor of Medicine Chair)

  2. Division of Comparative Medicine, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    James G. Fox (Director, Professor) (Director, Professor)

  3. Immunity and Environment Murdoch Childrens Research Institute, Royal Melbourne Hospital Footscray, Melbourne, Australia

    Andrew S. Giraud (Professor and Research Theme Director Infection) (Professor and Research Theme Director Infection)

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Azuma, T. (2009). Role of CagA in Helicobacter pylori Infection and Pathology. In: Wang, T.C., Fox, J.G., Giraud, A.S. (eds) The Biology of Gastric Cancers. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69182-4_15

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